Ultrasound-microbubble-mediated NF-kappaB decoy transfection attenuates neointimal formation after arterial injury in mice

J Vasc Res. 2006;43(1):12-8. doi: 10.1159/000089103. Epub 2005 Oct 20.

Abstract

Objective: Decoy transfection is a significant methodology for suppressing gene activation. The decoy can be synthesized easily; however, the major obstacle is the difficulty involved in effective in vivo delivery.

Methods and results: We used a fluorescein-labeled decoy to investigate the ultrasound-microbubble-mediated in vivo delivery in normal and injured mouse arteries. We showed that this approach could deliver the decoy into target tissues. In addition, we performed in vivo NF-kappaB decoy transfection into murine injured arteries using the ultrasound-microbubble method. Murine femoral arteries were injured using flexible wires to establish arterial injury. Pathologically, neointima/media areas in the NF-kappaB decoy transfection using ultrasound-microbubble group showed less than those in the control groups. Immunohistochemistry revealed that enhanced expression of inflammatory factors was observed in nontreated injured arteries, while the NF-kappaB decoy suppressed the expression.

Conclusion: We revealed that ultrasound-microbubble delivery of the decoy is effective for transfection into target organs. We also indicated that NF-kappaB decoy transfection using this method has potential for the suppression of neointimal formation. Ultrasound-mediated transfection of the decoy can be beneficial for the clinical treatment of restenosis after coronary intervention and other cardiovascular diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Femoral Artery / immunology
  • Femoral Artery / injuries*
  • Femoral Artery / pathology
  • Genetic Therapy / methods*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microbubbles*
  • NF-kappa B / genetics*
  • Transfection / methods*
  • Tunica Intima / immunology
  • Tunica Intima / pathology
  • Ultrasonics*
  • Vasculitis / immunology
  • Vasculitis / pathology

Substances

  • NF-kappa B